Our group has generated a panel of mice with deficiencies of either TNF or LT separately in T, B cells or macrophages/granulocytes. TNF and especially LT expressed by B cells is critical for development of functional architecture of spleen, but not of lymph nodes. The distinct features in this panel of conditional knock-out is being correlated with the expression pattern of specific genes, including lymphoid tissue chemokines and adhesion molecules. Additionally, we have generated mice with combined p53.TNF/LT deficiency and observed that the deletion of TNF/LT locus results in significant extension of the life span of p53-/- mice.